{"doi":"10.1093/nar/gkaf1523","title":"Visualization and quantification of rDNA instabilities in mammalian cells and mouse models","abstract":"Ribosomal DNA (rDNA) encodes the 18S, 5.8S, and 28S rRNA, accounting for ∼70% of cellular transcription. Despite its essential role and links to cancer and aging, quantifying rDNA instability in mammals remains challenging due to its repetitive organization and inherent heterogeneity. Here, we developed a murine rDNA FISH probe and genomic tools tailored for laboratory mouse strains. The results confirmed rDNA cluster locations, revealed substantial inter- and intra-strain as well as intercellular heterogeneity in rDNA organization within inbred mice and unstressed cells, and identified sources of spontaneous and replication-associated DNA double-strand breaks in the rDNA transcription termination region. Using mouse embryonic stem cells, we showed that BRCA1-mediated homologous recombination promotes rDNA instability, the non-homologous end joining factor XRCC1, but not Ku, suppresses intra-cluster deletions, and ATM kinase preserves rDNA cluster stability. Together, these findings establish a platform and tools for studying rDNA instability in animal models relevant to aging and cancer research.","journal":"Nucleic Acids Research","year":2025,"id":587733,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9482,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":281173,"name":"Wenxia Jiang","orcid":"0000-0002-5097-0975","position":1,"is_corresponding":false},{"id":246623,"name":"Wei Wu","orcid":"0000-0001-5164-2765","position":2,"is_corresponding":false},{"id":1503845,"name":"B. W. Lee","orcid":null,"position":3,"is_corresponding":false},{"id":512053,"name":"Demis Menolfi","orcid":"0000-0002-3824-9931","position":4,"is_corresponding":false},{"id":246620,"name":"Anthony Tubbs","orcid":"0000-0002-5605-8231","position":5,"is_corresponding":false},{"id":1503846,"name":"Olivia M. Cupo","orcid":null,"position":6,"is_corresponding":false},{"id":685178,"name":"Eli Malkovskiy","orcid":"0000-0002-9027-7497","position":7,"is_corresponding":false},{"id":994072,"name":"Mattie R. Nester","orcid":null,"position":8,"is_corresponding":false},{"id":313047,"name":"Xiaobin S. Wang","orcid":null,"position":9,"is_corresponding":false},{"id":225061,"name":"Peter A. Sims","orcid":"0000-0002-3921-4837","position":10,"is_corresponding":false},{"id":641919,"name":"Chyuan‐Sheng Lin","orcid":"0000-0002-6318-3743","position":11,"is_corresponding":false},{"id":121498,"name":"L S Symington","orcid":null,"position":12,"is_corresponding":false},{"id":248586,"name":"André Nussenzweig","orcid":null,"position":13,"is_corresponding":false},{"id":1503847,"name":"Brian M. McStay","orcid":null,"position":14,"is_corresponding":false},{"id":281177,"name":"Shan Zha","orcid":"0000-0002-6568-1818","position":15,"is_corresponding":false},{"id":1190495,"name":"Xi Zhu","orcid":"0000-0003-0502-8478","position":0,"is_corresponding":true}],"reference_count":97,"raw_metadata":null,"created_at":"2026-07-19T02:59:39.958043Z","pmid":"41533570","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}